STATus and Context within the Mammalian Nervous System

Prithi Rajan

doi:10.2119/molmed.2010.00259

Abstract

Effective manipulation of human disease processes may be achieved by understanding transcriptional, posttranscriptional and epigenetic events that orchestrate cellular events. The levels of activation of specific molecules, spatial distribution and concentrations of relevant networks of signaling molecules along with the receptiveness of the chromatin to these signals are some of the parameters which dictate context. Effects elicited by the transcription factor signal transducers and activator of transcription 3 (Stat3) are discussed with respect to the context within which Stat3-mediated effects are elicited within the developing and adult mammalian nervous system. Stat3 signals are pivotal to the proliferation and differentiation of neural stem cells. They also participate in neuronal regeneration and cancers of the nervous system. An analysis of the context in which Stat3 activation occurs in these processes provides a potential predictive paradigm with which novel methods for intervention may be designed.

Highlights

signal transducers and activator of transcription 3 (Stat3) was discovered as a transcription factor present in complexes which activated the promoters of interferon responsive genes [1], and as a transcription factor which was activated as a result of the acute phase response of liver cells [2,3]
This study showed that, at high concentration of ciliary neurotrophic factor (CNTF), Stat3 is activated by Janus kinases (JAKs) and extracellular signal regulated kinases (ERKs) which causes suppression of the neuronal pathway and leads to glial differentiation to Muller cells, while low concentrations of CNTF result in bipolar neuron differentiation, probably due to an ERK-mediated expression of transcription factors which promote neuronal differentiation
While Stat3 signals are activated during neural stem cells (NSCs) proliferation and differentiation into glial and neuronal fates, the context within which the activation is realized dictates the outcome

Summary

Introduction

Stat3 was discovered as a transcription factor present in complexes which activated the promoters of interferon responsive genes [1], and as a transcription factor which was activated as a result of the acute phase response of liver cells [2,3]. Predictions of interactions, and perhaps outcomes, of complex signaling cascades have been modeled in response to various stimuli [22], and the use of microarray-based technologies have yielded astonishing amounts of data describing transcription factor complexes and genes which are induced as a result of Stat3 activation in specific cellular systems, including stem cells [23,24].

Results

Conclusion